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On December 22, 2006, the Food and Drug Administration approved Radiesse, an injectable (under the skin) implant to restore or correct signs of facial lipidatrophy, or fat loss, in people with human immunodeficiency virus (HIV). Radiesse, a sterile, semi-solid cohesive implant consisting of synthetic calcium hydroxylapatite suspended in a gel carrier, is a medical device. It is already approved for use as a tissue marker, for treatment of vocal fold insufficiency, and to correct certain dental defects.
The safety and effectiveness of RADIESSE for the treatment of facial lipoatrophy was evaluated in a prospective, open-label, multi-center study of 100 patients with human immunodeficiency virus and facial lipoatrophy. Study subjects were at least 18 years of age, HIV positive, with a CD4 count ≥ 250 /mm3 and viral load ≤ 5000 copies/mL, had been receiving HAART therapy for a minimum of 3 years, and had HIV-associated facial lipoatrophy that was a grade 2, 3, or 4 on the Facial Lipoatrophy Severity Scale. The study population consisted predominantly of multi-ethnic, non-smoking males (94% male) with a mean age of 48 years. Forty-four (44) percent of patients were Black, Hispanic or Asian. Fifty-six (56) percent were Caucasian.
Patients received an initial treatment (initial injection and an additional injection at 1 month as needed). Six months later, all patients were assessed for the need for a touch up injection. Effectiveness was assessed at 3, 6 and 12 months from initial treatment by means of a Global Aesthetic Improvement Scale (GAIS) rating, cheek skin thickness measurements, and patient satisfaction assessment. Safety was assessed by the recording of adverse events through 12 months.
All treatments were performed with a 25 gauge, 1½ inch needle. Mean initial treatment volumes were 4.8mL for the initial treatment and 1.8mL at 1 month if necessary (85% of patients were treated at 1 month). At 6 months, the mean touch up volume was 2.4mL (89% of patients). Four (4) percent of patients received only one treatment, 18% of patients received a total of two treatments and 78% of patients received a total of three treatments. No patient received more than three treatments.
Mean left cheek thickness measurements at baseline was 4.7mm (N=100). At 3 months, the mean thickness was 7.3mm (N=100), representing an increase of 2.6 mm from baseline, with p-Value = 0.0001. At 6 months the mean thickness was 7.1mm (N=97), representing an increase of 2.4 mm from baseline, with a p-Value = 0.0001.
Mean cheek thickness at baseline for the right cheek was 4.9 mm (N=100). At 3 months, the mean thickness was 8.0 mm (N=100), representing an increase of 2.1 mm from baseline, with a p-Value of 0.0001. At 6 months the mean thickness was 7.5 mm (N=97), representing an increase of 2.7 mm from baseline, with a p-Value of 0.0001.
The most common adverse events reported were temporary edema (swelling), ecchymosis (bruising), erythema (reddening) and/or pain at the injection site.
The calcium hydroxylapatite (CaHA) particles in Radiesse can be seen in X-rays and CT Scans. It is important that patients inform their doctor and other health care professionals that they have had Radiesse injected in the face. In a radiographic study of 58 patients, there was no indication that RADIESSE potentially masked abnormal tissues or was interpreted as tumors in CT Scans.
Radiesse is a product of BioForm Medical Inc., of Franksville, WI.
Richard Klein
HIV/AIDS Program Director
Food and Drug Administration
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The Food and Drug Administration, on December 19, 2006, granted tentative approval for efavirenz Capsules, 50 mg, 100 mg, and 200 mg., manufactured by Aurobindo Pharma Limited Inc., of Hyderabad, India.
This is a generic version of the already-approved Sustiva Capsules, 50 mg, 100 mg, and 200 mg, manufactured by Bristol Myers Squibb Co.
Efavirenz is a member of the class of drugs known as nonnucleoside reverse transcriptase inhibitors (NNRTIs), which help keep the AIDS virus from reproducing. This antiretroviral drug is intended to be used in combination with other antiretroviral agents for the treatment of HIV-1 infection.
The application was reviewed under expedited review provisions for the President's Emergency Plan for AIDS Relief (PEPFAR).
Tentative Approval means that FDA has concluded that a drug product has met all required quality, safety and efficacy standards, though it may not yet be marketed in the U.S. because of existing patents and/or exclusivity rights. This tentative approval, however, does make the product eligible for consideration for purchase under the PEPFAR program.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
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Following these instructions is important for everyone, but especially for those most vulnerable to foodborne illness- including those with weakened immune systems due to conditions such as HIV/AIDS.
The U. S. Food and Drug Administration (FDA) reminds consumers to pay special attention to the handling of eggs and preparation of foods that contain eggs during this holiday season. Some holiday favorites, such as cookie dough, homemade eggnog, and some types of stuffing, may contain eggs that are raw or undercooked. Eggs sometimes contain a bacteria called Salmonella enteriditis (SE), which can cause illness if eggs are not handled and cooked properly. An FDA national survey of consumer food safety practices, the 2006 FDA/FSIS Food Safety Survey, found that cookie dough is one of the major sources of raw egg in the American diet, and that only three percent of respondents always use a food thermometer when they cook baked egg dishes such as stuffing.
To avoid egg-related illness from holiday foods:
An estimated 118,000 illnesses per year are caused by consumption of eggs contaminated with SE. To help consumers avoid these illnesses, FDA requires the following statement on packages of fresh eggs that have not been treated to destroy Salmonella:
Safe Handling Instructions: To prevent illness from bacteria;
Find more information about holiday food safety at www.cfsan.fda.gov or call 1-888-SAFEFOOD.
Richard Klein
HIV/AIDS Program Director
Food and Drug Administration
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Following these instructions is important for everyone, but especially for those most vulnerable to foodborne illness- including those with weakened immune systems due to conditions such as HIV/AIDS.
The U. S. Food and Drug Administration (FDA) reminds consumers to pay special attention to the handling of eggs and preparation of foods that contain eggs during this holiday season. Some holiday favorites, such as cookie dough, homemade eggnog, and some types of stuffing, may contain eggs that are raw or undercooked. Eggs sometimes contain a bacteria called Salmonella enteriditis (SE), which can cause illness if eggs are not handled and cooked properly. An FDA national survey of consumer food safety practices, the 2006 FDA/FSIS Food Safety Survey, found that cookie dough is one of the major sources of raw egg in the American diet, and that only three percent of respondents always use a food thermometer when they cook baked egg dishes such as stuffing.
To avoid egg-related illness from holiday foods:
An estimated 118,000 illnesses per year are caused by consumption of eggs contaminated with SE. To help consumers avoid these illnesses, FDA requires the following statement on packages of fresh eggs that have not been treated to destroy Salmonella:
Safe Handling Instructions: To prevent illness from bacteria;
Find more information about holiday food safety at www.cfsan.fda.gov or call 1-888-SAFEFOOD.
Richard Klein
HIV/AIDS Program Director
Food and Drug Administration
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FDA Proposes Rules to Expand Availability of Investigational Drugs and Clarify Permissible Charges to Patients
In an effort to enable more patients who lack satisfactory alternatives to have access to unapproved medicines, while balancing the need to safeguard the individual patient and ensure the continued integrity of the scientific process that brings safe and effective drugs to the market, on December 11, 2006, FDA proposed significant regulatory changes to make investigational drugs more widely and easily available to seriously ill patients, including those with HIV/AIDS, who have no other treatment options. The proposed changes also seek to clarify the specific circumstances and the types of costs for which a manufacturer can charge for an investigational drug made available for the purpose of treatment.
FDA would like to increase awareness in the healthcare community of the range of options available for obtaining investigational drugs for seriously ill patients, encourage companies to make such drugs available, and reduce barriers to obtaining them.
The proposed rule defines three categories of patients to whom investigational drugs could be made available for the purpose treatment outside of a clinical trial through expanded access, when there is no satisfactory alternative therapy, and defines requirements and safeguards for each. They are
FDA has allowed many types of access to investigational therapies since the 1970's. Some of the larger programs, including those under the treatment IND (Investigational New Drug) regulations, enabled tens of thousands of patients with HIV/AIDS, cancer and cardiovascular diseases to receive promising therapies before the products were approved for marketing. However, the existing regulations do not adequately describe the full range of programs available, explicitly recognizing only emergency use for individual patients and widespread treatment use access for large groups of patients. The proposed changes are meant to clearly reflect the full range of treatment use programs available, and ensure broad and equitable access to investigational drugs for treatment use.
The current regulations describing when it is appropriate to charge for an investigational drug need revisions because they fail to account for the full range of circumstances in which charging should be permissible and because they have proven difficult to interpret in practice, resulting in confusion over what costs could be recovered by sponsors making drug products available through expanded access programs.
The proposed rules, which are open for comment for 90 days, are described in detail at www.fda.gov/cder/regulatory/applications/IND_PR.htm.
The most significant proposed changes would:
(1) Modernize applicable regulations to include all circumstances under which access to investigational drugs is permitted, including:
(2) Make investigational drugs more widely available in appropriate situations by establishing criteria that link the level of evidence needed to support the use of an investigational drug to the seriousness of the disease and the number of patients likely to be treated with the drug in an expanded access program;
(3) Revise the current regulation regarding manufacturers' recovery of the costs of an investigational drug to:
The proposal also would simplify the cost recovery calculation by making clear that charges for an investigational drug used in a clinical trial may include only direct costs associated with the drug's development, and that charges for investigational drugs for treatment use may also include administrative costs of making the drug available for intermediate patient populations and under large scale treatment INDs.
Written comments, identified by Docket No. 2006N-0062 and RIN 0910-AF14 (for expanded access proposals) and Docket No. 2006N-0061 and/or RIN 0910-AF13, (for cost recovery proposals), are encouraged, and may be submitted by any of the following methods:
Richard Klein
HIV/AIDS Program Director
Office of Special Health Issues
Food and Drug Administration
Today, December 1, is World AIDS Day. This year's international theme is "Stop AIDS: Keep the Promise."
Started in 1988, World AIDS Day represents many things to many people. For some, it's about increasing awareness of HIV/AIDS, or an opportunity to remember those lost to AIDS, while others see World AIDS Day as an opportunity to rekindle our commitment to fighting the epidemic. UNAIDS estimates well over 50 Million people have been afflicted worldwide by HIV/AIDS since the start of the epidemic 25 years ago.
Many subscribers to this list serve are personally touched by the epidemic, either through their work, volunteer activities, as patients, or through friends and family affected by the disease. World AIDS Day is a time for all of us to take stock of our accomplishments, and pride in our contribution to the considerable progress that has been made. While many goals remain to be reached, the progress to date has been nothing short of extraordinary.
Over the past 25 years, FDA has worked hard to "keep the promise." In collaboration with our colleagues in industry, academia, and the patient and advocacy communities, FDA has been a part of the great wheel of progress against this disease, and helped to keep the wheel in motion.
FDA's HIV/AIDS-related responsibilities are summarized at http://www.fda.gov/oashi/aids/fdarole.html
A list of the 2006 FDA HIV-related accomplishments can be found at http://www.fda.gov/oashi/aids/listserve/archive.html#2006
A timeline of all significant FDA HIV-related activities is available on the web at http://www.fda.gov/oashi/aids/miles.html
Please take a moment today, December 1, to commemorate World AIDS Day in whatever way is meaningful to you, and take pride in the immense and varied contribution we have all made to the fight against this global pandemic.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
The Food and Drug Administration (FDA) is warning healthcare professionals regarding the significantly increased risk for serious and life-threatening cardiovascular (CV) complications associated with normalization of hemoglobin levels in patients receiving erythropoiesis-stimulating agents (ESAs).
Epoetin alfa is indicated for the treatment of anemia related to zidovudine therapy in HIV patients.
Information for Healthcare Professionals
Erythropoiesis Stimulating Agents (ESA)
Aranesp (darbepoetin), Epogen (epoetin alfa), and Procrit (epoetin alfa)
FDA is issuing this alert to advise you of a newly published clinical study showing that patients treated with an erythropoiesis-stimulating agent (ESA) and dosed to a target hemoglobin concentration of 13.5 g/dL are at a significantly increased risk for serious and life threatening cardiovascular complications, as compared to use of the ESA to target a hemoglobin concentration of 11.3 g/dL. The "Correction of Hemoglobin and Outcomes in Renal Insufficiency" (CHOIR) study, published November 16, 2006 in the New England Journal of Medicine, reports the adverse cardiovascular complications as a composite of the occurrence of one of the following events: death, myocardial infarction, hospitalization for congestive heart failure, or stroke.
The CHOIR study findings underscore the importance of following the currently approved prescribing information for Procrit, Epogen, and Aranesp, including the dosing recommendation that the target hemoglobin not exceed 12 g/dL.
This information reflects FDA's current analysis of data available to FDA concerning these drugs. FDA intends to update this sheet when additional information or analyses become available.
To report any serious adverse events associated with the use of these drugs, please contact the FDA MedWatch program via the web at https://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm
Considerations
Physicians and other healthcare professionals should consider the following when using erythropoiesis stimulating agents:
For all patients:
Information for the Patient
Physicians and other healthcare professionals should discuss the following with their patients:
Data Summary
Safety concerns related to the use of erythropoiesis-stimulating agents in the treatment of the anemia of chronic renal failure (CRF) is the topic of two clinical studies and an editorial published in The New England Journal of Medicine on November, 16, 2006. The 1,432 subject CHOIR study demonstrated increases in serious and potentially life threatening cardiovascular events when epoetin alfa (Procrit) is administered to reach higher target hemoglobin levels than lower target hemoglobin levels. The 603 subject CREATE study showed a trend toward more cardiovascular events in a pattern similar to the CHOIR study, thus supporting the findings of the CHOIR study. The CREATE study examined the use of epoetin beta, a product not approved in the USA.
The CHOIR study was a randomized, open label design in which anemic chronic kidney disease (CKD) subjects were randomized to be dosed to either a higher average target hemoglobin (13.5 g/dL) or a lower average target hemoglobin (11.3 g/dL). All subjects received Procrit. The primary endpoint was a time to event analysis for a composite cardiovascular endpoint (all cause mortality, congestive heart failure (CHF) hospitalization, non-fatal MI, or non-fatal stroke).
Procrit was administered as 10,000 Units SC weekly and titration allowed to a maximum dose of 20,000 Units weekly.
Overall, 715 subjects were randomized to the high target hemoglobin (13.5 g/dL) and 717 randomized to the low target hemoglobin (11.3 g/dL). At the end of the study, the average hemoglobin was 12.6 g/dL for the high group and 11.3 g/dL for the low group.
The composite cardiovascular endpoint was statistically worse in the higher target hemoglobin group with a hazard ratio of 1.3 [95% CI 1.03, 1.74] (p = 0.03 by log rank test).
The rates for the individual components of the composite primary endpoint were (high target vs. low):
| Event | Rate Comparison |
|---|---|
| Death | 7.3% vs 5.0% (p = 0.07) |
| CHF hosp | 9.0% vs 6.6% (p = 0.07) |
| Non-fatal MI | 2.5% vs 2.8% |
| Non-fatal stroke | 1.7% vs 1.7% |
The analyses for this study found no correlation between rate of rise of hemoglobin and adverse cardiovascular events. However, the relationship between seizures and the rate of rise of hemoglobin as reported in the labeling for all three products remains a concern.
The CHOIR and CREATE study findings underscore the importance of the existing warnings regarding cardiovascular risks that include thrombotic events and increased mortality observed in hemodialysis patients with cardiac disease targeted to higher hemoglobin levels (~14 g/dL), and recommendations not to exceed hemoglobin levels of 12 g/dL in approved labeling for Procrit, Epogen, and Aranesp. Please refer to the full prescribing information for additional information. Internet links to the full prescribing information for all approved ESA products may be found at the FDA page for this alert.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
On November 17, 2006, the Food and Drug Administration (FDA) granted tentative approval for a new fixed drug combination of stavudine/lamivudine/nevirapine tablets manufactured by Cipla Limited, of Mumbai, India. This product was reviewed under expedited procedures for the President's Emergency Plan for AIDS Relief (PEPFAR) program.
Stavudine, lamivudine, and nevirapine are anti-viral drugs for the treatment of HIV-1 infection. This product represents a new combination which can significantly decrease pill burden and could result in improved compliance for HIV infected individuals.
FDA's tentative approval of this product means that although existing patents and/or exclusivity prevent marketing of this product in the United States, the product has been shown to meet all of FDA's safety, efficacy, and manufacturing quality standards required for marketing in the U.S., and thus qualifies for consideration for purchase under PEPFAR.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
The Food and Drug Administration (FDA), on November 6, 2006, granted tentative approval for a generic formulation of abacavir sulfate tablets, 300 mg, manufactured by Cipla Limited of Mumbai, India. The application was reviewed under the expedited review provisions of the President's Emergency Plan for AIDS Relief (PEPFAR).
FDA's tentative approval means that although existing patents and/or exclusivity prevent marketing of this product in the United States, the product meets all of the safety, efficacy, and manufacturing quality standards required for marketing in the U.S., and can thus be considered for purchase under PEPFAR.
As with all generic applications, FDA conducts an on-site inspection of each manufacturing facility and of the facilities performing the bioequivalence studies prior to granting approval or tentative approval to these applications to evaluate the ability of the manufacturer to produce a quality product and to assess the quality of the bioequivalence data supporting the application.
This tentatively approved product, a generic version of Ziagen tablets manufactured by GlaxoSmithKline, is a nucleoside reverse transcriptase inhibitor (NRTI) for use in combination with other antiretroviral agents in the treatment of HIV infection.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
The Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection have been revised. The revision represents a major rewriting of the main document to improve its organization and readability. Because the main document has been almost completely rewritten, there is no highlighting of changes to either its text or tables.
The document's Appendix: Characteristics of Available Antiretroviral Drugs, and Supplement I: Pediatric Antiretroviral Drug Information, have also been updated. Changes to those sections appear highlighted in yellow.
Changes in recommendations include:
Also new to the guidelines are:
The updated guidelines are available on the Pediatric Guidelines page of the Clinical Guidelines section of AIDSinfo.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
The Food and Drug Administration (FDA) announced, on October 18, 2006, the availability of a guidance for industry entitled "Fixed Dose Combinations (FDC), Co-Packaged Drug Products and Single Entity Versions of Previously Approved Antiretrovirals for the Treatment of HIV." The guidance encourages sponsors to develop various drug product versions of previously approved antiretroviral drugs and encourages sponsors to submit drug applications for these products to FDA for review. The availability of a wide range of safe and effective antiretroviral drug products is hoped to facilitate a wider distribution of anti-HIV drugs to better meet the demands of the global HIV/AIDS pandemic.
The draft version of this guidance entitled "Fixed Dose Combination and Co-Packaged Drug Products for Treatment of HIV," was first posted on May 2004.
The guidance has been updated to address public comments to the draft version. Significant changes to the draft are: 1) the inclusion of single entity versions, in addition to combination products, in the expedited FDA review pathway for these products 2) the addition of tables that supply references supporting the clinical efficacy and safety of antiretroviral combinations 3) the inclusion of more details and clarification on the amount and type of data that should be submitted in a drug application to support a potential approval or tentative approval.
The full guidance is available on the FDA web site www.fda.gov/cder/guidance/6360fnl.pdf (343 KB).
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
On October 16, 2006, the Food and Drug Administration approved a new 300 mg capsule form of Reyataz (atazanavir).
Reyataz is now available as 100mg, 150 mg, 200 mg, and the new 300 mg capsules.
The new 300 mg capsules give treatment-experienced patients the option to take either one 300 mg capsule, or two 150 mg capsules of Reyataz, once daily plus ritonavir 100 mg once daily, with food.
The recommended dose for treatment-naïve patients remains unchanged and is Reyataz 400 mg (two 200mg capsules) once daily with food.
Reyataz is a product of Bristol-Myers Squibb.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
On October 10, 2006, the DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents released a new revision of the Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents.
The following are among changes that have been made to the May 4, 2006 version of the guidelines:
The following tables have been updated:
The complete October 10, 2006, version of the adult treatment guidelines is available on the AIDSinfo web site at http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Changes will be found highlighted in yellow.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
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The Food and Drug Administration, on October 5, 2006, granted tentative approval for didanosine for Oral Solution (Pediatric Powder), 10 mg/mL, manufactured by Aurobindo Pharma Limited Inc., of Hyderabad, India.
This is a generic version of the already-approved Videx Pediatric Powder for Oral Solution, 10 mg/mL, manufactured by Bristol Myers Squibb.
The application was reviewed under expedited review provisions for the President's Emergency Plan for AIDS Relief (PEPFAR).
"Tentative Approval" means that FDA has concluded that a drug product has met all required quality, safety and efficacy standards, though it may not yet be marketed in the U.S. because of existing patents and/or exclusivity rights. Tentative approval, however, does make the product eligible for consideration for purchase under the PEPFAR program.
Didanosine is a member of the class of drugs known as nucleoside reverse transcriptase inhibitors (NRTIs), which help keep the AIDS virus from reproducing. This antiretroviral drug is intended to be used in combination with other antiretroviral agents for the treatment of HIV-1 infection.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
The Food and Drug Administration (FDA) announced the approval, on October 5, 2006, of the APTIMA(r) HIV-1 RNA Qualitative Assay, manufactured by Gen-Probe Incorporated of San Diego, California, for use in clinical laboratories and public health facilities to detect primary (early) HIV-1 infection.
The APTIMA® HIV-I RNA Qualitative Assay is an in vitro nucleic acid test (NAT) for the detection of human immunodeficiency virus (HIV-1) in human plasma intended for use as an aid in the diagnosis of HIV-I infection, including acute or primary infection, before the appearance of antibodies to HIV-1.
Traditional detection and diagnosis of HIV-I infection is based on testing for anti-viral antibodies by enzyme immunoassay (EIA) with confirmation by supplemental antibody tests such as Western blot or immunofluorescence assays (IFA). Although sensitivity of HIV-1 antibody detection has increased in the last few years, a window period between infection and detectable serological markers still exists. Following a recent exposure to HIV-I, it may take several months for the antibody response to reach detectable levels, during which time, testing for antibodies to HIV-I, including the use of rapid antibody tests, will not indicate true infection status.
The newly approved test may provide earlier diagnosis of infection because it detects nucleic acid of the human immunodeficiency virus (HIV-1) in human plasma, rather than the antibody response to the virus. Presence of HIV-I RNA in the plasma of patients without antibodies to HIV-I is indicative of acute or primary HIV-1 infection.
The test, however, is not meant to be used as a stand-alone test for the diagnosis of HIV-1 infection. A positive nucleic acid test should be viewed as a unconfirmed test result, indicating probable infection, and should be followed up later with traditional EIA antibody testing to confirm infection with the Human Immunodeficiency Virus.
In addition, the APTIMA HIV-1 RNA Qualitative Assay may be used as an additional test to confirm HIV-I infection in an individual whose specimen is repeatedly reactive for HIV-1 antibodies. This is important because the Western blot can, in some instances, be difficult to interpret and may not always provide a conclusive result. The APTIMA test can be used instead of the traditional Western blot test or IFA for confirmation of HIV-1 infection when the screening test result for HIV-1 antibodies is positive.
The sensitivity of the APTIMA(r) HIV-1 RNA Qualitative Assay is comparable to that of FDA approved viral load assays that measure the amount of HIV-1 virus circulating in the blood of patients with established HIV-1 infection to monitor the treatment and progression of AIDS. Unlike the viral load tests, however, the APTIMA test has been approved for the diagnosis of primary HIV-1 infection, as well as for confirming HIV-1 infection when tests for antibodies to HIV-1 are positive.
The product labeling for this test will be available soon on the list of FDA Licensed/Approved HIV, HTLV and Hepatitis Tests on the FDA web site.
Richard Klein Office of Special Health Issues
Food and Drug Administration
The Food and Drug Administration (FDA), on September 13, 2006, granted tentative approval for a fixed dose tablet containing lamivudine/zidovudine 150 mg/300 mg manufactured by Cipla Limited of Mumbai, India. The tablets are indicated for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults.
Tentative approval means that FDA has concluded that a drug product has met all of the required quality, safety and efficacy standards, though it may not be marketed in the U.S. due to existing patents and/or exclusivity rights. However, tentative approval makes the product eligible to be considered for purchase under the President's Emergency Plan for AIDS Relief (PEPFAR) program.
The lamivudine/zidovudine fixed dose combination tablets are a version of the FDA approved Combivir tablets manufactured by GlaxoSmithKline.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
The Food and Drug Administration (FDA) will hold a public meeting of its Antiviral Drugs Advisory Committee on October 19 and 20, 2006,to discuss design issues in the development of products for treatment of chronic Hepatitis C, including co-infection with HIV.
The meeting will be held on October 19, 2006, from 8 a.m. to 4 p.m. and on October 20, 2006, from 8 a.m. to 4 p.m. at the Hilton Washington DC/Silver Spring, 8727 Colesville Rd., Silver Spring, MD, 20910 in The Ballrooms. Please note that meeting will be closed to the public on October 20 from 1 p.m. to 4 p.m., to permit discussion and review of trade secret and/or confidential information.
On both days, the committee will discuss clinical trial design issues in the development of products for the treatment of chronic hepatitis C infection. This meeting is being convened in response to the growing number of products in development for this indication. The primary objectives for committee deliberations are to discuss issues related to the identification of appropriate control arms, populations for study, endpoints, and long-term follow-up. As noted above, on October 20, 2006, the meeting will be open to the public from 8 a.m. to 12 noon, unless public participation does not last that long, and closed to the public from 1 - 4 p.m.
Background material will become available no later than 1 business day before the meeting and will be posted on FDA's Web site at www.fda.gov/ohrms/dockets/ac/acmenu.htm. (Click on the year "2006" and scroll down to the Antiviral Drugs Advisory Committee meeting.)
Interested parties may submit comments electronically on line at www.fda.gov/dockets/ecomments. Select "2006N-0219--Clinical Trial" and follow the prompts to submit your statement.
Written comments may be submitted to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852, by close of business on October 5, 2006.
All comments received will be posted without change, including any personal information provided. Comments received on or before October 5, 2006, will be provided to committee members before the meeting.
Oral presentations from the public (the open public hearing section of the meeting) will be scheduled between approximately 1 p.m. and 2 p.m. on October 19, 2006. Time allotted for each presentation may be limited depending on the number of requests to speak. Those desiring to make formal oral presentations should notify the contact person (below) on or before October 5, 2006, and submit a brief statement of the general nature of the evidence or arguments they wish to present, the name(s) and contact information of the proposed speaker(s), and an indication of the approximate time requested to make their presentation.
Contact Person: Cicely Reese, Center for Drug Evaluation and Research (HFD-21), Food and Drug Administration, 5600 Fishers Lane, (for express delivery, 5630 Fishers Lane, rm. 1093), Rockville, MD 20857, 301-827-7001, FAX: 301-827-6776, e-mail: cicely.reese@fda.hhs.gov
For up-to-date information about the meeting, please use the FDA Advisory Committee Information Line, 1-800-741-8138 (301-443-0572 in the Washington, DC area), and enter code no. 3014512531.
FDA welcomes the attendance of the public at its advisory committee meetings and will make every effort to accommodate persons with physical disabilities or special needs. If you require special accommodations due to a disability, please contact Cicely Reese at least 7 days in advance of the meeting.
No registration is necessary.
Persons attending FDA's advisory committee meetings are advised that the agency is not responsible for providing access to electrical outlets.
If you need hotel accommodations or directions, please contact the hotel directly at 301-589-5200.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
On August 28, 2006, FDA granted tentative approval for stavudine capsules, 30 mg and 40 mg, manufactured by Strides Acrolab Ltd., Bangalore, India, under the expedited review provisions created for the President's Emergency Plan for AIDS Relief (PEPFAR).
FDA's tentative approval means that although the product meets all of the safety, efficacy, and manufacturing quality standards required for marketing in the U.S., existing patents and/or exclusivity currently prevent marketing of this product in the United States. Tentative approval, however, qualifies the product for consideration for purchase under the PEPFAR program.
As with all generic applications, FDA conducts an on-site inspection of each manufacturing facility and of the facilities performing the bioequivalence studies prior to granting approval or tentative approval to these applications to evaluate the ability of the manufacturer to produce a quality product and to assess the quality of the bioequivalence data supporting the application.
This product is a generic version of Zerit Capsules, 30 mg and 40 mg, a nucleoside reverse transcriptase inhibitor (NRTI) used in combination with other antiretroviral agents for the treatment of HIV-1 infection, manufactured by Bristol-Myers Squibb.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
The Food and Drug Administration (FDA), on August 23, 2006, granted tentative approval for a fixed dose tablet containing lamivudine/zidovudine 150 mg/300 mg manufactured by Pharmacare Limited of South Africa. The tablets are indicated for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults.
Tentative approval means that FDA has concluded that a drug product has met all of the required quality, safety and efficacy standards, though it may not be marketed in the U.S. due to existing patents and/or exclusivity rights. However, tentative approval makes the product eligible to be considered for purchase under the President's Emergency Plan for AIDS Relief (PEPFAR) program.
The lamivudine/zidovudine fixed dose combination tablets are a version of the FDA approved Combivir tablets manufactured by GlaxoSmithKline.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
FDA granted tentative approval, on August 11, 2006, for Nevirapine tablets, 200 mg, manufactured by Strides Acrolab Ltd., Bangalore, India. This action represents the first product manufactured by Strides Acrolab to receive tentative approval for a generic formulation of a therapy for HIV/AIDS from the FDA. It is, however, the fourth generic formulation of Nevirapine to receive tentative approval from FDA under the expedited review provisions created for the President's Emergency Plan for AIDS Relief (PEPFAR).
FDA's tentative approval means that although existing patents and/or exclusivity prevent marketing of this product in the United States, the product meets all of the safety, efficacy, and manufacturing quality standards required for marketing in the U.S., and can be considered for purchase under PEPFAR.
As with all generic applications, FDA conducts an on-site inspection of each manufacturing facility and of the facilities performing the bioequivalence studies prior to granting approval or tentative approval to these applications to evaluate the ability of the manufacturer to produce a quality product and to assess the quality of the bioequivalence data supporting the application.
This product is a generic version of Viramune tablets manufactured by Boehringer Ingelheim, a non-nucleoside reverse transcriptase inhibitor (NNRTIs) used in combination with other antiretroviral agents for the treatment of HIV-1 infection.
The use of single dose nevirapine for the prevention of mother to child transmission of HIV is permitted under PEPFAR.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
The Food and Drug Administration is advising consumers to avoid eating raw oysters harvested in the Pacific Northwest as a result of increased reports of illnesses associated with the naturally occurring bacteria Vibrio parahaemolyticus (Vp) in oysters harvested from the area. Oysters harvested from this region have been reported to cause gastrointestinal illness. The threat is particularly important for people who have compromised immune function, including those living with HIV/AIDS.
Until the threat of Vp from oysters harvested in the Pacific Northwest has passed, consumers are advised to thoroughly cook oysters harvested from that area before eating. They also should thoroughly cook oysters if they are not certain of the oysters' origin, or if they wish to further reduce their risk of infection from bacteria that may be found in raw oysters.
In recent months, there has been an unusual increase in bacterial illness associated with eating raw oysters from the Pacific Northwest. The illnesses are associated with the naturally occurring bacterium Vp, which is most prevalent during summer months when water temperatures in the Pacific Northwest are most favorable for its growth. While Vp can cause mild gastrointestinal disorders in healthy individuals, those with weak immune systems and older persons are at greater risk for serious more illness, such as septicemia (infection of the blood system).
Pacific Northwest oysters are distributed nationally. Although to date most of the illnesses reported have occurred in the Pacific Northwest, some have been reported in New York state as well.
In Washington state, shellfish control authorities are identifying and closing areas where people have become sick from eating oysters. Washington state has initiated a recall of all shell stock oysters (oysters in the shell) harvested from areas closed within the state. Because of the potential for nationwide distribution, consumers are advised to follow recall instructions and return associated shell stock oysters to the retailer from which they were purchased.
Cooking destroys the bacteria, eliminating the risk of illness for both healthy and immunocompromised individuals. The majority of illnesses that occur from the consumption of raw oysters are not life-threatening to the general population and commonly range from mild intestinal disorders of short duration to acute gastroenteritis. The symptoms are watery diarrhea, often with abdominal cramping, nausea, vomiting, fever and chills. Usually these symptoms occur within 24 hours of ingestion and last no more than three days. Severe disease is rare and occurs most commonly in persons with weakened immune systems.
Persons with weakened immune systems, including those affected by AIDS; and persons with chronic alcohol abuse, liver, stomach or blood disorders, cancer; diabetes, or kidney disease should avoid raw oyster consumption altogether, regardless of where the oysters are harvested.
Consumers can continue to enjoy oysters in many cooked preparations by following this advice.
At Restaurants and other Food Service Establishments:
In the shell:
Shucked Oysters:
For further information contact:
FDA Food Safety Hotline: 1-888-SAFEFOOD
Richard Klein
HIV/AIDS Program Director
Office of Special Health Issues
Food and Drug Administration
The Food and Drug Administration granted tentative approval on July 26, 2006 for lamivudine/zidovudine tablets, co-packaged with abacavir sulfate tablets, for treatment of HIV, manufactured by Aurobindo Pharma Limited Inc., of Hyderabad, India.
The lamivudine/zidovudine combination is a generic formulation of the approved combination product, Combivir, manufactured by GlaxoSmithKline, which combines the two Nucleoside Reverse Transcriptase Inhibitors (NRTIs) in a single tablet. Abacavir sulfate, which is also an NRTI, is a generic formulation of the approved product, Ziagen, also manufactured by GlaxoSmithKline.
The application was reviewed under expedited review provisions for the President's Emergency Plan for AIDS Relief (PEPFAR).
"Tentative Approval" means that FDA has concluded that a drug product has met all required quality, safety and efficacy standards, though it may not be marketed in the U.S. because of existing patents and/or exclusivity rights. Tentative approval, however, does make the product eligible for consideration for purchase under the PEPFAR program.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
Return to Index
Important notification regarding the Vironostika HIV-1 test kit
bioMerieux, Inc. has become aware of five HIV-1 finished kit lots in the field which have been reported to contain EnzAbody reagent that appears noticeably cloudy and/or flocculent, instead of clear and non-turbid as expected 30 minutes after reconstitution.
Kit lot numbers identified are 121566, 121567, 121568, 160342, and 160339 with EnzAbody Lot Numbers of 1008926, 1008926, 1008926, 1011220 and 1011021 respectively.
bioMerieux is asking all customers to verify the appearance of the EnzAbody reagent prior to using it in an assay as a general practice for all lots, whether or not they appear in this list.
If the EnzAbody reagent appears to be noticeably cloudy and/or flocculent 30 minutes after reconstitution, as a precaution, the reagent should not be used to perform the assay. Use of cloudy EnzAbody could possibly increase your risk of inaccurate HIV test results in patients and therefore should be avoided.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
The Food and Drug Administration (FDA) today (July 12, 2006) approved Atripla Tablets, a new fixed-dose combination of three widely used antiretroviral drugs, to be taken in a single tablet once a day, alone or in combination with other antiretroviral products for the treatment of HIV-1 infection in adults. Atripla is the first fixed dose combination available in the United States to combine two different classes of antiviral drugs in a single pill. This "one-pill-once-a-day" product to treat HIV/AIDS combines the active ingredients of Sustiva (efavirenz) a Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI), with Emtriva (emtricitabine) and Viread (tenofovir disoproxil fumarate), two Nucleoside Reverse Transcriptase Inhibitors (NRTIs). Emtriva and Viread are also available in a fixed dose combination known as Truvada.
Atripla is the result of an unprecedented inter-company cooperative effort between Gilead Sciences, the manufacturer of Emtriva and Viread, with Bristol-Myers Squibb, the manufacturer of Sustiva. Merck controls the marketing of Sustiva outside the United States. The approval of Atripla will not only make the new fixed dose combination available in the U.S., but also permit its purchase under the President's Emergency Plan for AIDS Relief (PEPFAR) program.
Atripla was approved in 3 months under FDA's fast track program. The approval is the result of an expedited review process outlined in guidance for industry from the FDA in May 2004. http://www.fda.gov/oc/initiatives/hiv/hivguidance.html The guidance encourages manufacturers to develop fixed dose combination and co-packaged products consisting of previously approved antiretroviral therapies for the treatment of HIV infection.
The drug combination represented by this product is a recommended first line regimen for treatment naive patients (except during first trimester of pregnancy or in women with high pregnancy potential) in the national Guidelines for the Use of Antiretroviral agents in HIV-1-Infected Adults and Adolescents (http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf).
Atripla can significantly simplify a drug treatment regimen by reducing the pill burden, helping to increase adherence and thus reducing potential development of viral resistance to the drugs. This may result in longer term effectiveness of the regimen..
Since the three components of Atripla have been in use for some time, their characteristics and effects are well known. In addition, the safety and effectiveness of the combination of these three drugs were shown in a 48 week-long clinical study with 244 HIV-1 infected adults receiving the drugs contained in Atripla. In this trial, 80 percent of the participants achieved a marked reduction of the human immunodeficiency virus and a substantial increase in the number of healthy CD4 cells.
The labeling of Atripla includes a boxed warning that the drug's use can cause lactic acidosis (buildup of an acid in the blood). In patients with chronic Hepatitis B infection, the discontinuation of the treatment with Atripla (which is not indicated for this use) can result in severe flare-ups of Hepatitis B infection. Other potential serious adverse events reported for the use of Atripla's ingredients include serious liver toxicity, renal impairment and severe depression. The most common adverse events experienced by participants in the combination trial included headache, dizziness, abdominal pain, nausea, vomiting, and rash.
FDA approved Sustiva in 1998, Viread in 2001 and Emtriva in 2003. Truvada, which combined Viread and Emtriva in a fixed dose combination, was approved in 2004.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
The Public Health Service Task Force Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV-1 Transmission in the United States has been revised to include an update of the "Antiretroviral Drug Resistance and Resistance Testing in Pregnancy" section to reflect new recommendations for resistance testing for HIV-infected pregnant women.
The Perinatal Working Group now recommends resistance testing for 1) all pregnant women not currently receiving antiretrovirals, before starting treatment or Mother To Child Transmission (MTCT) prophylaxis, and 2) all pregnant women receiving antenatal antiretroviral therapy who have virologic failure or who have sub-optimal viral suppression after initiation of antiretroviral therapy.
The Working Group also counsels against adding single-dose maternal/infant NVP to an ongoing highly active antiretroviral regimen, as this does not provide additional efficacy in reducing perinatal transmission and may result in NVP drug resistance in the mother.
Information in Table 6 from the November 17, 2005 document has been updated and replaced with a recommendation box at the beginning of the "Antiretroviral Drug Resistance and Resistance Testing in Pregnancy" section; the old Table 6 has been removed and the remaining tables have been renumbered accordingly.
The updated section and new references are highlighted in the document.
The document is available in the "Guidelines" section of the AIDSinfo Web site under " Perinatal Guidelines." You can download the guidelines or can request to receive them by e-mail or regular mail on the AIDSinfoWeb site.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
The Food and Drug Administration, on July 10, 2006, granted tentative approval for didanosine tablets (chewable, dispersible, buffered), 100 mg, 150 mg and 200 mg, manufactured by Aurobindo Pharma Limited Inc., of Hyderabad, India.
This is a generic version of the already-approved Videx Chewable Tablets manufactured by Bristol Myers Squibb.
The application was reviewed under expedited review provisions for the President's Emergency Plan for AIDS Relief (PEPFAR).
"Tentative Approval" means that FDA has concluded that a drug product has met all required quality, safety and efficacy standards, though it may not yet be marketed in the U.S. because of existing patents and/or exclusivity rights. Tentative approval, however, does make the product eligible for consideration for purchase under the PEPFAR program.
Didanosine is a member of the class of drugs known as nucleoside reverse transcriptase inhibitors (NRTIs), which help keep the AIDS virus from reproducing. This antiretroviral drug is intended to be used in combination with other antiretroviral agents for the treatment of HIV-1 infection.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
On June 30, 2006, Boehringer Ingelheim and FDA informed Healthcare Professionals about important new findings related to Aptivus (tipranavir) capsules, co-administered with ritonavir, 500mg/200mg. Boehringer Ingelheim identified 14 reports of intracranial hemorrhage (ICH) events, including 8 fatalities, in 6,840 HIV-1 infected individuals receiving Aptivus capsules in combination antiretroviral therapy in clinical trials.
Many of the patients experiencing ICH in the Aptivus clinical development program had other medical conditions (CNS lesions, head trauma, recent neurosurgery, coagulopathy, hypertension or alcohol abuse) or were receiving concomitant medications, including anticoagulants and antiplatelet agents, that may have caused or contributed to these events. An increased risk of ICH was previously observed in patients with advanced HIV-1 disease/AIDS. Further investigations are ongoing to assess the role of Aptivus in ICH.
No pattern of abnormal coagulation parameters were observed in patients receiving Aptivus in general, or preceding the development of ICH. Routine measurement of coagulation parameters is not currently indicated in the management of patients on Aptivus. However, in in vitro experiments, tipranavir was observed to inhibit human platelet aggregation at levels consistent with exposures observed in patients receiving Aptivus/ritonavir.
According to the Dear Healthcare Provider letter, APTIVUS/ritonavir should be used with caution in patients who may be at risk for increased bleeding from trauma, surgery or other medical conditions, or who are receiving medications known to increase the risk of bleeding such as antiplatelet agents or anticoagulants.
Information on ICH risk and platelet aggregation inhibition findings will be included in the following sections of the Package Insert:
The new Black Box Warning reads:
"APTIVUS CO-ADMINISTERED WITH 200 MG RITONAVIR HAS BEEN ASSOCIATED WITH REPORTS OF BOTH FATAL AND NON-FATAL INTRACRANIAL HEMORRHAGE. (SEE WARNINGS) APTIVUS CO-ADMINISTERED WITH 200 MG RITONAVIR HAS BEEN ASSOCIATED WITH REPORTS OF CLINICAL HEPATITIS AND HEPATIC DECOMPENSATION INCLUDING SOME FATALITIES. EXTRA VIGILANCE IS WARRANTED IN PATIENTS WITH CHRONIC HEPATITIS B OR HEPATITIS C CO-INFECTION, AS THESE PATIENTS HAVE AN INCREASED RISK OF HEPATOTOXICITY. (SEE WARNINGS)"
A pdf copy of the Dear Healthcare Provider letter is available in pdf format on the FDA web site at http://www.fda.gov/medwatch/safety/2006/Aptivus-tipranavir_DHCP.pdf
The revised product labeling is available in pdf format at http://www.fda.gov/medwatch/safety/2006/Aptivus_PI.pdf
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Jeffrey Murray
Division of Antiviral Products
Food and Drug Administration
The Food and Drug Administration (FDA), on June 30, 2006, issued the first tentative approval for a fixed-dose, three-ingredient tablet for use as a complete anti-viral treatment of human immunodeficiency virus (HIV-1) infection in adults. The product, (lamivudine-zidovudine-nevirapine tablet), contains the active ingredients in the widely used antiretroviral drugs Epivir (lamivudine), Retrovir (zidovudine) and Viramune (nevirapine). The combination tablet is manufactured by Aurobindo Pharma Ltd. in Hyderabad, India.
The recommended regimen for the lamivudine-zidovudine-nevirapine tablet is one pill twice a day following an initial two week treatment with the individual components taken individually. Each ingredient of this generic tablet is currently approved to treat HIV-1 infected adults in combination with other antiretroviral agents. The safety and effectiveness of the combination of lamivudine-zidovudine-nevirapine in lowering the viral load and increasing the CD4+ cell has been demonstrated in previously conducted adequate and well controlled studies of the individual ingredients being used together for treatment.
The labeling of the combination drug includes a medication guide and a boxed warning that the drug’s use can cause liver failure, severe rash, and lactic acidosis (buildup of an acid in the blood).
Under the PEPFAR program, the FDA may grant a tentative approval if it concludes that a drug product has met all of the required clinical safety and efficacy and manufacturing quality standards for marketing in the United States. However, because of existing patents and/or exclusivity rights protecting the individual innovator products, the fixed dose combination product cannot be sold on the United States at this time.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Products
Food and Drug Administration
The Food and Drug Administration, on June 27, 2006, granted tentative approval for Abacavir Sulfate Oral Solution, 20 mg/mL, manufactured by Aurobindo Pharma Limited Inc., of Hyderabad, India.
This is a generic version of the already-approved Ziagen brand of the product manufactured by GlaxoSmithKline .
The application was reviewed under expedited review provisions for the President's Emergency Plan for AIDS Relief (PEPFAR).
"Tentative Approval" means that FDA has concluded that a drug product has met all required quality, safety and efficacy standards, though it may not yet be marketed in the U.S. because of existing patents and/or exclusivity rights. Tentative approval, however, does make the product eligible for consideration for purchase under the PEPFAR program.
Abacavir sulfate is a member of the class of drugs known as nucleoside reverse transcriptase inhibitors (NRTIs), which help keep the AIDS virus from reproducing. This antiretroviral drug is intended to be used in combination with other antiretroviral agents for the treatment of HIV-1 infection.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
The Food and Drug Administration, on June 27, 2006, granted tentative approval for stavudine 15 and 20 mg capsules manufactured by Aurobindo Pharma Limited Inc., of Hyderabad, India. Tentative approval was granted to the same manufacturer for generic stavudine, 30 and 40 mg capsules on July 1, 2005, and for Oral Solution, 1 mg/mL on December 21, 2006.
This is a generic version of the already-approved Zerit brand of the product manufactured by Bristol Myers-Squibb.
The application was reviewed under the expedited review provisions for the President's Emergency Plan for AIDS Relief (PEPFAR).
Tentative Approval means that FDA has concluded that a drug product has met all required quality, safety and efficacy standards, though it may not yet be marketed in the U.S. because of existing patents and/or exclusivity rights. Tentative approval, however, does make the product eligible for consideration for purchase under the President's Emergency Plan for AIDS Relief (PEPFAR) program.
Stavudine is a member of the class of drugs called Nucleoside Reverse Transcripts Inhibitors (NRTIs) which helps keep the AIDS virus from reproducing. Stavudine is used in combination with other antiretroviral agents for the treatment of HIV-1 infection.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
The Food and Drug Administration, on June 23, 2006, granted accelerated approval for Prezista (darunavir - formerly known as TMC-114), a new drug for treatment experienced adults whose infection with the human immunodeficiency virus (HIV) is not responding to treatment with other antiretroviral drugs. Prezista, a protease inhibitor, is indicated to be co-administered with a low-dose of ritonavir, in combination with other active anti-HIV agents. Ritonavir, which is also a protease inhibitor, slows the metabolism of Prezista, resulting in increased plasma concentrations. The recommended oral dose of Prezista tablets is 600 mg (two 300 mg tablets) twice daily taken with ritonavir 100 mg twice daily and with food. The type of food does not affect exposure to darunavir.
The accelerated approval is based on evidence from two randomized, controlled studies comparing the safety and effectiveness of a Prezista-ritonavir combination with other ritonavir-boosted protease inhibitor combinations. Patients in both arms of these trials also used other anti-HIV agents (nucleoside reverse transcriptase inhibitors) with or without enfuvirtide, a fusion inhibitor that inhibits the virus from entering the cell. In these studies, patients on a Prezista-ritonavir combination experienced higher rates of reduction of their HIV viral load than patients on other ritonavir-boosted protease inhibitor combinations. Seventy percent of treatment-experienced patients achieved a virologic response with PREZISTA/ritonavir in combination therapy compared to 21 percent in control group at week 24.
The most common side effects reported by patients on the Prezista-ritonavir regimen included diarrhea, nausea, and headache. About seven percent of patients on this combination therapy experienced skin rashes ranging from mild to serious.
The risks and benefits of Prezista have not been established for adults who have not been previously treated for HIV, or for children.
As a condition of the accelerated approval, the manufacturer is required to conduct post-marketing trials to verify and describe the clinical benefits of Prezista. In addition, the manufacturer has committed to conducting other postmarketing studies that include studies in pediatric populations, studies to better define certain drug-drug interactions, and to evaluate the drug in patients with varying degrees of liver impairment to identify appropriate dosing for this patient population.
Prezista is manufactured for Tibotec, Inc., Division of Ortho Biotech Products, L.P., Raritan, N.J., by JOLL, Gurabo, Puerto Rico.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Jeffery Murray
Division of Antiviral Products
Food and Drug Administration
Return to Index
The Food and Drug Administration (FDA) granted tentative approval on June 22, 2006 for generic lamivudine - oral solution, 10 mg/mL manufactured by Cipla Limited, Mumbai, India. This action represents the second tentative approval of a generic version of the already FDA approved Epivir Oral Solution, 10 mg/mL, manufactured by GlaxoSmithKline. This child-friendly-product is indicated for use in pediatric patients with HIV from three months to 16 years.
Tentative approval for a generic lamivudine oral solution was first granted on November 4, 2005 to a formulation produced by another manufacturer in India.
Lamivudine is in the class of drugs called nucleoside reverse transcriptase inhibitors (NRTIs), which help keep the AIDS virus from reproducing. This antiretroviral drug is intended to be used in combination with other antiretroviral agents for the treatment of HIV-1 infection.
FDA's tentative approval of this product means that although existing patents and/or exclusivity prevent marketing of this product in the United States, the product meets all of FDA's safety, efficacy, and manufacturing quality standards required for marketing in the U.S. and it will now be available for consideration for purchase under the President's Emergency Plan for AIDS Relief (PEPFAR).
Richard Klein
HIV/AIDS Program Director
Office of Special Health Issues
Food and Drug Administration
FDA published, this week, a final Guidance for Industry on Antiviral Product Development--Conducting and Submitting Virology Studies to the Agency to assist sponsors in the development of antiviral drugs and biological products (i.e., therapeutic proteins and monoclonal antibodies) from the initial pre-IND through the new drug application (NDA) and postmarketing stages.
The guidance serves as a starting point for understanding what nonclinical and clinical virology data are important to support the submission of an Investigational New Drug Application (IND), New Drug Application (NDA), or Biologics License Application (BLA) for approval of an antiviral product. The guidance focuses on nonclinical and clinical virology study reports and makes recommendations for collecting and submitting resistance data to the Food and Drug Administration (FDA). Nonclinical and clinical virology study reports, based on collected data, are essential for FDA's review of antiviral drug investigational and marketing applications. Specific topics discussed in the guidance include:
The guidance document, and specific topic attachments are available on the FDA web site through the following links:
The Guidance
Attachment -Submitting HIV Resistance Data
The
Guidance Attachment- Submitting Influenza Resistance Data
The Guidance Attachment-
Submitting HBV Resistance Data
The Guidance Attachment-
Submitting HCV Resistance Data
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
FDA/Forum for Collaborative HIV Research Collaborative Meeting on Long-Term Safety Concerns Associated with CCR5 Antagonist Development
Wednesday, May 31, 2006
The Forum for Collaborative HIV Research and the FDA's Division of Antiviral
Products will host an open public meeting on May 31, 2006 to discuss issues
regarding the development of CCR5 co-receptor antagonists for the treatment
of HIV infection. Specific issues for discussion are mechanisms for
long-term follow-up to monitor safety of patients enrolled in CCR5 antagonist
clinical trials, potential consequences of viral tropism changes, and characterization
of resistance to these investigational agents.
WEBCAST INFORMATION FOR THOSE NOT ABLE TO ATTEND IN PERSON:
Free Webcast Set-up:
(Before the meeting the link will state PENDING and on the day of the meeting the link will state VIEW WEBCAST
If you have any problems or need help: please call us at 301.984.0001 or email: support@FDALive.com
**The webcast will be accessible up to one year after the meeting for future
reference**
FOR THOSE WHO ARE ABLE TO ATTEND IN PERSON:
The meeting will be held from 8:30am - 4:15pm in the Continental Ballroom and
Amphitheater on the 3rd floor of The George Washington University Marvin Center
(The Marvin Center, 800 21st Street, N.W., Washington, DC 20052). For information
regarding directions, parking, etc. please go to http://gwired.gwu.edu/marvincenter/info/Address/.
The final agenda and a list of Background Documents are available on the Forum's website at www.hivforum.org. We will have a limited number of copies at the meeting so we would prefer participants to view the documents beforehand or to make their own copies if possible.
Registration/check-in will begin at 8:00 am outside of the Continental Ballroom. We will also have an overflow room (Amphitheater-next to Continental Ballroom) which will allow those who are not able to sit inside the Continental Ballroom to view the meeting via webcast.
Lunch will not be provided; however, there are plenty of area restaurants/eateries
that you can walk to. Across from the Marvin Center, the shops at 2000 Penn
offer a variety of places to eat. Please visit their website for ideas - http://www.2000penn.com/wheretoeat.html.
Lunch will be from 12:30 - 1:30pm.
If you should have any questions pertaining to the meeting on the 31st, please
contact Becky Griesse at blg@gwu.edu or
at 202-416-0494.
Richard Klein
HIV/AIDS Program Director
Office of Special Health Issues
Food and Drug Administration
The Food and Drug Administration (FDA) granted, on May 18, 2006, tentative approval for a generic version of abacavir sulfate tablets, 300 mg, manufactured by Aurobindo Pharma LTD. of Hyderabad, India. Abacavir sulfate tablets are the first generic version of the already approved Ziagen Tablets, an anti-HIV medication manufactured by GlaxoSmithKline. Tentative approval makes this product available for consideration for purchase under the President's Emergency Plan for AIDS Relief (PEPFAR).
Abacavir is a nucleoside reverse transcriptase inhibitor (NRTI), a class of drugs that helps keep the AIDS virus from reproducing. It is used in combination with other antiretroviral agents for the treatment of HIV-1 infection.
The agency's tentative approval means that Aurobindo's product meets all of FDA's manufacturing quality and clinical safety and efficacy standards, but existing patents and/or exclusivity prevent its marketing in the United States at this time.
Richard Klein
HIV/AIDS Program Director
Office of Special Health Issues
Food and Drug Administration
FDA is issuing guidance providing recommendations to sponsors regarding data to support the: 1) Initiation of pediatric studies of a preventive HIV vaccine under a United States (U.S.) investigational new drug application (IND); and 2) licensure of a preventive HIV vaccine for pediatric use. The guidance also provides recommendations to investigators and institutional review boards (IRBs) who are involved with these pediatric studies.
This guidance specifically addresses issues regarding development of a preventive HIV vaccine for use in healthy U.S. pediatric populations. The guidance is available on the FDA web site at http://www.fda.gov/cber/gdlns/pedhiv.htm. Copies of this guidance are also available from the Office of Communication, Training and Manufacturers Assistance (HFM-40), 1401 Rockville Pike, Suite 200N, Rockville, MD 20852-1448, or by calling 1-800-835-4709 or 301-827-1800.
Written comments on this guidance may be submitted at any time to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. Submit electronic comments to www.fda.gov/dockets/ecomments. You should identify all comments with the title of this guidance, Development of Preventive HIV Vaccines for Use in Pediatric Populations.
Richard Klein
HIV/AIDS Program Director
Office of Special Health Issues
Food and Drug Administration
The Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents has been revised to include up-to-date treatment information, including new recommendations for resistance testing, treatment interruption, and HBV/HIV co-infection. Tables have been revised to include up-to-date information about drug interactions and about the lopinavir/ritonavir 200/50 mg tablet formulation. Changes to the document are summarized in the "What's New in the Document?" section, and all changes to the document are highlighted in yellow throughout the text.
The updated guidelines document is available in the ADULT GUIDELINES section of the GUIDELINES page on the www.AIDSinfo.nih.gov web site. The site also contains an option to order hard copies of the guidelines or request an electronic copy by e-mail.
AIDSinfo is also a useful source of other information related to HIV/AIDS, including other treatment and prevention guidelines, downloadable databases for PDAs (Personal Digital Assistants), and HIV/AIDS-related clinical trials information.
Richard Klein
HIV/AIDS Program Director
Office of Special Health Issues
Food and Drug Administration
This message corrects the previous (3/29/2006) notice of a tentative approval for the 100 mg capsule dosage form of zidovudine to treat HIV/AIDS. While the generic formulation does qualify for consideration under the President's Emergency Fund for AIDS Relief (PEPFAR), because patents on the original formulations have expired, FDA has issued an approval for generic zidovudine capsules to be marketed in the United States. The tablet and oral solution dosage forms of zidovudine were previously approved for sale in the United States when the patent on those dosage forms expired in September 2005. The approval for the capsule formulation of the drug, which is manufactured by Aurobindo Pharma LTD. in Hyderabad, India, follows the expiration of GlaxoSmithKline's patent on its capsule form of the product marketed under the tradename Retrovir.
Zidovudine is in the class of drugs called nucleoside reverse transcriptase inhibitors (NRTIs), which help keep the AIDS virus from reproducing. This anti-retroviral drug is intended to be used with other anti-retroviral agents for the treatment of HIV-1 infection.
The agency's approval of zidovudine means that there are no existing patents and/or exclusivity preventing the approval of generic versions of this product. As with all FDA-approved generics, this product must meet all of FDA's manufacturing quality, and clinical safety and effectiveness standards for U.S. marketing.
Richard Klein
HIV/AIDS Program Director
Office of Special Health Issues
Food and Drug Administration
The Food and Drug Administration, on March 27, 2006, granted tentative approval for zidovudine 100 mg capsules manufactured by Aurobindo Pharma Limited Inc., of Hyderabad, India. This is a generic version of the already-approved Retrovir brand of the product manufactured by GlaxoSmithKline.
The application was reviewed under the expedited review provisions of the President's Emergency Plan for AIDS Relief (PEPFAR).
Tentative Approval means that FDA has concluded that a drug product has met all required quality, safety and efficacy standards, though it may not yet be marketed in the U.S. because of existing patents and/or exclusivity rights. Tentative approval, however, does make the product eligible for consideration for purchase under the President's Emergency Plan for AIDS Relief (PEPFAR) program.
Zidovudine is in the class of drugs called nucleoside reverse transcriptase inhibitors (NRTIs), which help keep the AIDS virus from reproducing. This antiretroviral drug is intended to be used in combination with other antiretroviral agents for the treatment of HIV-1 infection.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
On March 8, 2006, FDA granted traditional approval to two tenofovir DF containing products manufactured by Gilead Sciences, VIREAD (tenofovir disoproxil fumarate) and TRUVADA (fixed dose combination of tenofovir DF and emtricitabine). Both products are indicated for the treatment of HIV in combination with other antiretroviral drugs.
VIREAD and TRUVADA had received accelerated approval on Oct. 26, 2001 and August 2, 2004, respectively. Traditional approval is supported by previously submitted studies and the recently submitted Study 934, which compared the antiviral activity of tenofovir DF, emtricitabine, and efavirenz to zidovudine, lamivudine and efavirenz in treatment naïve HIV-infected individuals receiving these regimens through 48 weeks.
The results of Study 934 are included in the updated package inserts of VIREAD
and TRUVADA. Highlights of the label changes are summarized in the attached
pdf file.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
The Food and Drug Administration (FDA) on March 6, 2006, granted tentative approval for a copackaged antiretroviral drug regimen, consisting of lamivudine/zidovudine fixed dose combination tablets and efavirenz tablets, for the treatment of HIV-1 infection in adults. It is manufactured by Aurobindo Pharma Ltd., Hyderabad, India. There is no predicate version of this co-packaged product approved in the United States.
FDA granted tentative approval for the generic formulation of efavirenz on June 24, 2005, and for the combination of lamivudine and zidovudine on July 7, 2005, both manufactured by Aurobindo Pharma LTD. Aurobindo Pharma's lamivudine/zidovudine fixed dose combination tablets are a version of the already FDA approved Combivir tablets manufactured by GlaxoSmithKline, and the efavirenz tablets are a version of Sustiva tablets manufactured by Bristol Myers-Squibb.
A Tentative Approval means that FDA has concluded that a drug product has met all required quality, safety and efficacy standards, though it may not yet be marketed in the U.S. due to existing patents and/or exclusivity rights. Tentative approval, however, does make the product eligible for consideration for purchase under the President's Emergency Plan for AIDS Relief (PEPFAR) program.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
Below is contextual information regarding the design of proposed studies to support marketing approval of Over-the-Counter (OTC) home-use HIV test kits which includes an historical overview of rapid HIV test kit approval in the United States, and key issues for consideration by the FDA Blood Products Advisory Committee. Once posted, transcripts of the March 10, 2006 advisory committee meeting will be available on the FDA website at http://www.fda.gov/ohrms/dockets/ac/cber06.html#BloodProducts
Issue
FDA seeks the advice of the Committee on proposed studies that would be needed to validate a home-use HIV test kit with regard to test accuracy, test interpretation, and medical follow-up based on the provision of informational material in place of a trained test operator and counselor.
Background
Rapid HIV Tests:
1. Sale is restricted to clinical laboratories
2. The test is approved for use only by an agent of a clinical laboratory.
3. Test subjects must receive a "Subject Information" pamphlet and pre-test counseling prior to specimen collection and appropriate counseling when test results are provided.
4. The test is not approved for use to screen blood, cell, plasma, or tissue donors.
Purchasers of the test receive a customer letter stating that by purchasing the test they agree to abide by these restrictions.
Home use tests:
Key Issues:
There are a number of potential benefits to home-use HIV test kits:
There are a number of potential risks associated with home-use HIV test kits:
Additional issues include:
Consideration of a home-use test kit by FDA will require the test kit manufacturer to demonstrate that the test is safe and effective.
History of FDA consideration of OTC for HIV tests:
FDA has discussed HIV home-use test kits and home-use collection kits over the past 10 years in various forums. This included communications with manufacturers of home collection systems in 1988-89, the BPAC in June 1994, and in Federal Register notices in 1989, 1990, 1995, and, most recently, in 2005 (Ref. 2-5).
In the course of discussions held prior to 2005, appropriate regulatory criteria were identified for home-use specimen collection kits for HIV testing, but not for home-use HIV test kits. With improved test kit technology (ease of use, freedom from biohazards, and excellent performance characteristics), we believe it may be feasible to identify regulatory criteria for home-use HIV test kit.
On November 3, 2005, FDA brought the issue of approaches to the validation of over-the-counter (OTC) home-use HIV test kits to BPAC for discussion in response to renewed interest in home-use HIV test kits.
At that meeting, the Committee heard presentations from OraSure Technologies for a home-use test kit based on its currently approved OraQuick ADVANCE Rapid HIV-1/2 Antibody Test when used with oral fluid specimens; from CDC on changes in HIV testing practices and counseling recommendations, including the role of rapid HIV tests in the HHS Advancing HIV Prevention initiative and the results of post-marketing surveillance for rapid HIV tests and home sample collection HIV tests; from CDC on quality system considerations for home-use HIV test kits; from an expert on psychological and social issues associated with HIV testing, including the finding that, although death from suicide is common among people with advanced HIV infection, notification of a positive HIV test does not appear to lead to a sudden and substantial rise in suicide death; and from CDRH on its review practice for OTC IVDs.
Eighteen individuals spoke at the Open Public Hearing, including those who spoke in favor of home-use HIV test kits, those against home-use HIV test kits, and those who recommended a cautious approach.
Committee discussions addressed acceptable levels of test performance, approaches to clinical trials to evaluate test performance in the hands of potential users, and the content of test kit informational materials that would be needed to allow the test to be performed in the absence of live counseling. By virtue of this discussion, the Committee acknowledged that criteria could be established to permit FDA approval of a home-use HIV test kit.
Discussion
What test characteristics favor possible approval of an OTC home-use HIV test?
What information will be discussed at the BPAC meeting?
After considering comments from the BPAC at the November 3, 2005 meeting, FDA has drafted a set of proposed studies to support the approval of home-use HIV test kits, addressing the following:
At this meeting, FDA will be presenting to the BPAC, for its comments and recommendations, details of the proposed studies needed to support approval of home-use HIV test kits.
Questions for the Committee
1. Does the Committee concur with FDA's proposed criteria for test performance
(analytical and clinical sensitivity and specificity) for home-use HIV test
kits?
2. Does the Committee concur with FDA's proposal for clinical studies that would be needed to validate the accuracy of a home-use HIV test kit?
3. Does the Committee concur with FDA's proposed content needed for informational materials provided with home-use HIV test kits and the steps that should be taken to validate the adequacy of those informational materials to communicate or provide pathways to adequately address issues including:
a. Accuracy of testing
b. Correct test interpretation
c. The importance of supplemental testing for confirmation of positive results
d. Management of psychological and social issues
e. Medical referral
4. If the Committee does not concur with any of the proposals in Questions 1-3, what additional information/modification would be needed to support approval of a home-use HIV test kit?
References
1. Blood Products Advisory Committee Sixty-Sixth Meeting, session on Development
of Rapid HIV tests, June 15, 2000. http://www.fda.gov/ohrms/dockets/ac/00/transcripts/3620t1.pdf
2. Federal Register, 2/17/89 (54 FR 7279), Blood Collection Kits Labeled for Human Immunodeficiency Virus Type 1 (HIV-1) Antibody Testing; Home Test Kits Designed to Detect HIV-1 Antibody; Open Meeting
3. Federal Register, 7/30/90 (55 FR 30982), Blood Collection Kits Labeled for Human Immunodeficiency Virus (HIV-1) Antibody Testing; Availability of a Letter for Interested Persons
4. Federal Register, 2/23/95 (60 FR 10087), Home Specimen Collection Kit Systems Intended for Human Immunodeficiency Virus (HIV-1 and/or HIV-2) Antibody Testing; Revisions to Previous Guidance
5. Blood Products Advisory Committee Sixty-Sixth Meeting, session on Approach to Validation of Over-the-Counter (OTC) Home-Use HIV Tests, November 3, 2005. http://www.fda.gov/ohrms/dockets/ac/05/transcripts/2005-4190t1.htm
Richard Klein
HIV/AIDS Program Director
Office of Special Health Issues
Food and Drug Administration
FDA's Center for Biologics Evaluation and Research (CBER) will discuss the design of proposed studies to support the approval of over-the-counter (OTC) home-use human immunodeficiency virus (HIV) test kits as part of a two-day meeting of FDA's Blood Products Advisory Committee. The discussion of proposed studies to support the approval of OTC Home-Use HIV Test Kits will take place on the morning of March 10, 2006, beginning at 8:30 a.m. at the Hilton Hotel, 620 Perry Parkway, Gaithersburg, MD, 20879, 301-977-8900.
There are two types of home-use tests: collection kits and test kits.
There is currently one FDA approved home-use collection kit on the market for HIV testing, where the user collects their own sample, mails it to a laboratory, and gets the result over the phone or in the mail.
Home-use tests are designed to be used at home by untrained persons without the help of a healthcare professional. Most home-use tests, such as tests for blood glucose, cholesterol, and pregnancy, are available OTC without a prescription. With a test kit, users collect their own sample, test the sample, and read/interpret their own result.
There are currently no home-use test kits approved for the detection of any infectious agent.
At the meeting, FDA will be seeking the advice of the Committee on proposed studies that would be needed to validate a home-use HIV test kit with regard to test accuracy, test interpretation, and medical follow-up based on the provision of informational material in place of a trained test operator and counselor.
Interested persons may present data, information, or views, orally or in writing, on issues pending before the committee. Written submissions may be made to Donald W. Jehn, or Pearline K. Muckelvene, Center for Biologics Evaluation and Research (HFM-71), Food and Drug Administration, 1401 Rockville Pike, Rockville, MD 20852. To speak at the open public hearing section of the meeting, please contact Donald W. Jehn, or Pearline K. Muckelvene, at 301-827-0314.
Additional information about the meeting may be obtained from the Federal Register announcement of the meeting at http://www.fda.gov/OHRMS/DOCKETS/98fr/E6-1075.htm or through the FDA Advisory Committee Information Line, 1-800-741-8138 (301-443-0572 in the Washington, DC area), code 3014519516.
FDA welcomes the attendance of the public at its advisory committee meetings and will make every effort to accommodate persons with physical disabilities or special needs. If you require special accommodations due to a disability, please contact Donald W. Jehn or Pearline K. Muckelvene at least 7 days in advance of the meeting.
Persons attending FDA's advisory committee meetings are advised that the agency is not responsible for providing access to electrical outlets.
Richard Klein
HIV/AIDS Program Director
Office of Special Health Issues
Food and Drug Administration
The Food and Drug Administration will be conducting a public workshop entitled "Behavior-Based Blood Donor Deferrals in the Era of Nucleic Acid Testing [NAT)." The workshop will provide an opportunity for public discussion on the scientific basis for behavior-based donor deferral criteria, and the value of their continued use now that nucleic acid based tests (NAT) are available for certain transfusion-transmissible agents.
Donor deferrals based on geographical, medical and behavioral factors associated with an increased risk for exposure to transfusion transmissible infectious diseases are a first line of defense against introducing newly emerging infectious agents into the blood supply. As tests are developed to detect evidence of infection with such agents, behavioral and other risk-based deferrals are generally retained, to provide additional protection, particularly for imperfect tests and imperfect inventory management. As more advanced tests become available, particularly the highly sensitive and specific NAT tests capable of directly detecting infectious agents in blood at very early stages during infection, a question arises whether specific risk factor based deferrals should be modified or even eliminated. In the case of behavior-based criteria, retention of the deferrals has raised concerns of a social as well as a scientific nature.
To enable FDA to assess the value of current behavior-based donor deferrals in this era of NAT testing for certain infectious agents and to consider the scientific basis for the retention or potential modification or elimination of those deferrals, FDA will attempt to bring timely data and current thinking to bear on several key issues.
The public workshop will feature presentations by national and international experts from government and academic institutions and industry. Discussions will include:
The workshop will be held on March 8, 2006, from 8 a.m. to 5:3O p.m. at the National Institutes of Health, Lister Hill Auditorium, NIH Building 38A, 8600 Rockville Pike, Bethesda, MD 20894.
Registration
There is no registration fee for this meeting; however, seating space is limited
to 176 attendees and early registration is recommended on or before February
17, 2006. On-site registration will be limited to space available on the
day of the workshop beginning at 7:30 a.m.
Please mail, fax, or e-mail your registration information (including name, title, firm name, address, and telephone and fax numbers) or use the registration form in this announcement and mail, fax or e-mail it to Rhonda Dawson, Food and Drug Administration, HFM-302, 1401 Rockville Pike, Rockville, MD 20852; Fax: 301-827-2843; E-mail: rhonda.dawson@fda.hhs.gov
If you need special accommodations due to a disability, please contact Rhonda Dawson at least 7 days in advance.
Regardless of attendance at the public workshop, interested persons may submit written or electronic comments regarding the public workshop to the Division of Dockets Management . Submit electronic comments to http://www.fda.gov/dockets/ecomments. Please submit two paper copies of any mailed comments, except that individuals may submit one paper copy, to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Room 1061, Rockville, MD 20852. Comments should be identified with "docket number 2006N-0045." Written or electronic comments may be submitted until May 8, 2006.
A transcript of the public workshop will be posted, when available, on the FDA web site at www.fda.gov/cber/minutes/workshop-min.htm
Please note - Under current security measures, non-National Institutes of
Health employees can gain access to the NIH campus by private car at only two
locations:
(1) NIH's South Drive, where it intersects Rockville Pike; and
(2) NIH's Center Drive, where it intersects Old Georgetown Road.
At these sites, cars will be inspected, and drivers and passengers must show
picture IDs in order to receive NIH visitor passes. Limited visitor pay parking
is available along Center Drive, in lots adjoining Building 38A (Lister Hill
Center) and Building 45 (Natcher).
Access to NIH by the Metro (subway stop is Medical Center, on the Red Line) is highly recommended.
Richard Klein
HIV/AIDS Program Director
Office of Special Health Issues
Food and Drug Administration
FDA and The Forum for Collaborative HIV Research have announced May 31, 2006 as the date of the open public meeting to discuss issues regarding the development of CCR5 co-receptor antagonists for the treatment of HIV infection.
As described in a November 21, 2005 list serve announcement, the purpose of this meeting will be to discuss issues regarding the development of CCR5 co-receptor antagonists for the treatment of HIV infection, specifically mechanisms for long-term follow-up of patients enrolled in CCR5 antagonist clinical trials, potential consequences of tropism changes, and characterization of resistance to these investigational agents.
Please consider contributing suggestions, your experiences and lessons learned from other long-term (>48 weeks) follow-up studies in HIV-infected subjects, as well as experiences from other therapeutic areas and innovative suggestions for collection of long-term safety data. This information will be used to formulate issues for presentation and discussion at the meeting.
To prepare for this meeting, we are requesting the following:
A. Tropism and Safety Issues:
* Are there other potential adverse effects to the immune system that require
additional monitoring? Please provide abstracts and/or publications (including
unpublished data and/or manuscripts in press) you think are relevant to this
topic.
B. Long-term Monitoring Plan - Currently the FDA is requesting five years
of follow-up for patients who experience virologic failure in phase II and
III CCR5 co-receptor antagonist studies. We recommend that sponsors evaluate
patients two-three times a year for CD4+ cell counts, viral load, viral tropism,
and occurrence of AIDS-defining illnesses and death.* What are the feasibility
concerns for the five-year follow-up commitment?
* What mechanisms can be used to ensure sufficient data collection and minimize
lost-to-follow-up?
* Please provide suggestions on adequate control groups for comparative safety
evaluation.
* Please provide proposals for data analyses for the long-term follow-up studies.
* Please provide additional alternative proposals for long-term monitoring,
including other disease models.
* What type of studies can be designed to further establish the relationship
between viral tropism and pathogenesis?
C. Resistance/Tropism Issues:
* Please comment on the amount and type of resistance/tropism information needed
at the time of approval of new CCR5 antagonists.
D. Other:
* Please comment on the role of CCR5 antagonists in the antiretroviral armamentarium.
* Please comment on the potential role of tropism/resistance testing in clinical
practice (e.g., routine, optional, none).
* Given the issues previously discussed are there any special/additional concerns
for pediatric drug development?
During the meeting we intend to differentiate between information needed at the time of approval versus post-approval and between academic/investigator-initiated studies. Please keep this distinction in mind as you prepare your responses.
Please send your responses to blg@gwu.edu.
Register for this meeting at http://www.hivforum.org/CCR5/signup_form.html
If you have any questions, please contact:
Rebecca Griesse
blg@gwu.edu
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
Updates to the REYATAZ (atazanavir sulfate) package insert were approved on January 25, 2006, to reflect new in vitro inhibition data and clinical drug-drug interaction information regarding coadministration of atazanavir and/or atazanavir/ritonavir with proton pump inhibitors, H2 receptor antagonists, methadone, rifampin, enteric-coated didanosine and tenofovir.
A summary of the changes to the package insert is provided in the attached pdf file.
The complete revised label is available at http://www.fda.gov/cder/foi/label/2006/021567s007lbl.pdf
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
The U.S. Food and Drug Administration (FDA) today (January 18, 2006) unveiled a major revision to the format of prescription drug information, including drugs to treat HIV/AIDS, commonly called the package insert or drug label, to make information for healthcare professionals clear and concise to help ensure safe and optimal use of drugs. Part of an effort to manage the risks of medication use and reduce medical errors, the newly designed package insert will provide the most up-to-date information in an easy-to-read format that draws attention to the most important pieces of drug information, thus reducing the complexity of information on prescription drug labels. The new format will also make prescription information more accessible for use with electronic prescribing tools and other electronic information resources.
The new drug labeling requirements will be phased in gradually, and initially will apply to newly and recently approved prescription drugs and drugs that receive approval for new uses. The agency is encouraging drug makers to consider complying with the new labeling requirements earlier on a voluntary basis. All drugs approved within the past five years are included, and they will gradually be converted to the new prescribing information format.
The new format requires that the prescription information for newly approved products and those approved within the last five years, meet specific graphical requirements, including the reorganization of critical information so physicians can find the information they need quickly. Some of the most significant changes include:
The most notable change is the addition of a summary, outlining the most important information about a product, prominently displayed at the top of the page to help healthcare professionals find the information they need quickly. This summary, called Highlights, will typically be half a page in length and will provide a concise summary of information about specific areas including: Boxed Warning, Indications and Usage, and Dosage and Administration; and will refer the healthcare professional to the appropriate section of the Full Prescribing Information. In addition, drug makers will be required to include a list of all substantive recent changes made within the year, to ensure healthcare professionals have immediate access to the most up-to-date information about the product before prescribing it.
A new Table of Contents will refer readers to detailed information located in the label. The Full Prescribing Information is reorganized to give greater prominence to the most important and most commonly referenced information. As a result of feedback from two national physician surveys, the Indications and Usage and the Dosage and Administration sections are moved to the beginning of the Full Prescribing Information.
The addition, a new Patient Counseling Information section places greater emphasis on the importance of communication between professionals and patients. This new section is designed to help doctors advise their patients about important uses and limitations of medications. It will also serve as a guide for discussions about the potential risks involved in taking a specific treatment and steps for managing those risks. If FDA has approved patient information for a prescription drug, it will be printed at the end of the label immediately following the Patient Counseling Information section or will accompany the label so it can be easily shared.
As prescription information is updated in this new format it will be added to a new online health information clearinghouse called DailyMed that will provide up-to-date medication information free to consumers, healthcare professionals and healthcare information providers. This information can be accessed through the National Library of Medicine at http://dailymed.nlm.nih.gov. Only one example is available at this time.
In the future, this new information will also be provided through a website called facts@fda, a comprehensive Internet resource designed to give one-stop access for information about all FDA-regulated products.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration